[Federal Register Volume 63, Number 132 (Friday, July 10, 1998)]
[Rules and Regulations]
[Pages 37246-37249]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-18406]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 175

[Docket No. 90F-0142]


Indirect Food Additives: Adhesives and Components of Coatings

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending the food 
additive regulations to provide for the safe use of polyurethane resins 
derived from the reaction of toluene diisocyanate or 4,4' 
methylenebis(cyclohexylisocyanate) with fumaric acid-modified 
polypropylene glycol or fumaric acid-modified tripropylene glycol, 
triethylamine, and ethylenediamine as a component of adhesives for 
articles intended to contact food. This action responds to a petition 
filed by Olin Corp.

DATES: The regulation is effective July 10, 1998. Submit written 
objections and requests for a hearing by August 10, 1998.

ADDRESSES: Submit written objections to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Daniel N. Harrison, Center for Food 
Safety and Applied Nutrition (HFS-215), Food and Drug Administration, 
200 C St. SW., Washington, DC 20204, 202-418-3084.

SUPPLEMENTARY INFORMATION:

I. Background

    In a notice published in the Federal Register of May 10, 1990 (55 
FR 19667), FDA announced that a food additive petition (FAP OB4201) had 
been filed by Olin Corp., 120 Long Ridge Rd., Stamford, CT 06904. The 
petition proposed to amend the food additive regulations in 
Sec. 175.105 Adhesives (21 CFR 175.105) to provide for the safe use of 
polyurethane resins derived from the reactions of toluene diisocyanate 
or 4,4' methylenebis(cyclohexylisocyanate) with carboxylic acid-
modified polypropylene glycol and with triethylamine and 
ethylenediamine as a component of adhesives for articles intended to 
contact food. In a notice published in the Federal Register of 
September 5, 1997 (62 FR 46979), FDA amended the May 10, 1990, notice 
to state that upon further review of the petition, the petitioner 
specifically requested the approval of the use of polyurethane resins 
derived from the reaction of toluene diisocyanate or 4,4' 
methylenebis(cyclohexylisocyanate) with fumaric acid-modified propylene 
glycol or fumaric acid-modified tripropylene glycol, triethylamine, and 
ethylenediamine.
    In its evaluation of the safety of this additive, FDA has reviewed 
the safety of the additive itself and the chemical impurities that may 
be present in the additive resulting from its manufacturing process. 
Although the additive itself has not been shown to cause cancer, it may 
contain minute amounts of toluenediamine (TDA), which is a carcinogenic 
impurity resulting from the manufacture of the additive. Residual 
amounts of impurities are commonly found as

[[Page 37247]]

constituents of chemical products, including food additives.

II. Determination of Safety

    Under the so-called general safety clause of the Federal Food, 
Drug, and Cosmetic Act (the act) (21 U.S.C. 348(c)(3)(A)), a food 
additive cannot be approved for a particular use unless a fair 
evaluation of the data available to FDA establishes that the additive 
is safe for that use. FDA's food additive regulations (21 CFR 170.3(i)) 
define safe as ``a reasonable certainty in the minds of competent 
scientists that the substance is not harmful under the intended 
conditions of use.''
    The food additives anticancer, or Delaney, clause of the act (21 
U.S.C. 348(c)(3)(A)) provides that no food additive shall be deemed 
safe if it is found to induce cancer when ingested by man or animal. 
Importantly, however, the Delaney clause applies to the additive itself 
and not to impurities in the additive. That is, where an additive 
itself has not been shown to cause cancer, but contains a carcinogenic 
impurity, the additive is properly evaluated under the general safety 
standard using risk assessment procedures to determine whether there is 
a reasonable certainty that no harm will result from the intended use 
of the additive (Scott v. FDA, 728 F.2d 322 (6th Cir. 1984)).

III. Safety of the Petitioned Use of the Additive

    FDA estimates that the petitioned use of the additive, polyurethane 
resins derived from the reaction of toluene diisocyanate or 4,4' 
methylenebis(cyclohexylisocyanate) with fumaric acid-modified 
polypropylene glycol or fumaric acid-modified tripropylene glycol, 
triethylamine, and ethylenediamine, will result in exposure to the 
additive that would be virtually nil (Ref. 1).
    FDA does not ordinarily consider chronic toxicological studies to 
be necessary to determine the safety of an additive whose use will 
result in such low exposure levels (Ref. 2), and the agency has not 
required such testing here. However, the agency has reviewed the 
available toxicological data on the additive and concludes that the 
``virtually nil'' dietary exposure resulting from the petitioned use of 
this additive is safe.
    FDA has evaluated the safety of this additive under the general 
safety standard, considering all available data and using risk 
assessment procedures to estimate the upper-bound limit of lifetime 
human risk presented by TDA, the carcinogenic chemical that may be 
present as an impurity in the additive. The risk evaluation of TDA has 
two aspects: (1) Assessment of exposure to the impurity from the 
proposed use of the additive; and (2) extrapolation of the risk 
observed in the animal bioassay to the conditions of exposure to 
humans.

A. Toluenediamine

    FDA has estimated the cumulative exposure to TDA from all currently 
regulated uses of the additives where TDA may be present as an impurity 
and from the petitioned use of the additive in polyurethane adhesive 
applications to be no more than 0.059 part per billion in the daily 
diet (3 kilograms) or 0.18 microgram (<greek-m>g)/person/day (Ref. 3). 
The agency used data from long-term rodent bioassays on 2,4' 
toluenediamine conducted by the National Cancer Institute (Ref. 4) to 
estimate the upper-bound limit of lifetime human risk from the 
cumulative exposure to this chemical resulting from the currently 
regulated food additive uses where TDA may be present as an impurity 
and the proposed use of the additive. The authors reported that the 
test material caused significant amounts of hepatocellular carcinomas 
in both male and female rats and carcinomas of the mammary gland in 
female rats. The test chemical was also carcinogenic for female mice, 
causing hepatocellular carcinomas.
    Based on the agency's estimate that exposure to TDA will not exceed 
0.18 <greek-m>g/person/day, FDA estimates that the upper-bound limit of 
lifetime human risk from all regulated uses of the additives where TDA 
may be present as an impurity and from the proposed use of the subject 
additive is 6.1 x 10<SUP>-7</SUP>, or 6 in 10 million (Ref. 5). Because 
of the numerous conservative assumptions used in calculating the 
exposure estimate, the actual lifetime-averaged individual exposure to 
TDA is likely to be substantially less than the estimated exposure, and 
therefore, the probable lifetime human risk would be less than the 
upper-bound limit of lifetime human risk. Thus, the agency concludes 
that there is reasonable certainty that no harm from exposure to TDA 
would result from the proposed use of the additive.

B. Need for Specifications

    The agency has also considered whether specifications are necessary 
to control the amount of TDA as an impurity in the food additive. The 
agency finds that specifications are not necessary for the following 
reasons: (1) Because of the low levels at which TDA may be expected to 
remain as an impurity following production of the additive, the agency 
would not expect this impurity to become a component of food at other 
than extremely low levels; and (2) the upper-bound limit of lifetime 
human risk from exposure to TDA is very low (6 in 10 million).

IV. Conclusion

    FDA has evaluated data in the petition and other relevant material. 
Based on this information, the agency concludes that the proposed use 
of the additive as a component of adhesives for articles intended to 
contact food is safe, and that the additive will achieve its intended 
technical effect. Therefore, the agency concludes that the regulations 
in Sec. 175.105 should be amended as set forth below.
    In accordance with Sec. 171.1(h) (21 CFR 171.1(h)), the petition 
and the documents that FDA considered and relied upon in reaching its 
decision to approve the petition are available for inspection at the 
Center for Food Safety and Applied Nutrition by appointment with the 
information contact person listed above. As provided in Sec. 171.1(h), 
the agency will delete from the documents any materials that are not 
available for public disclosure before making the documents available 
for inspection.

V. Paperwork Reduction Act of 1995

     This final rule contains no collection of information. Therefore, 
clearance by the Office of Management and Budget under the Paperwork 
Reduction Act of 1995 is not required.

VI. Environmental Impact

    The agency has carefully considered the potential environmental 
effects of this action. FDA has concluded that the action will not have 
a significant impact on the human environment, and that an 
environmental impact statement is not required. The agency's finding of 
no significant impact and the evidence supporting that finding, 
contained in an environmental assessment, may be seen in the Dockets 
Management Branch (address above) between 9 a.m. and 4 p.m., Monday 
through Friday. No comments were received during the 30-day comment 
period specified in the May 10, 1990, filing notice for comments on the 
environmental assessment submitted with the petition.

VII. Objections

    Any person who will be adversely affected by this regulation may at 
any time on or before August 10, 1998, file with the Dockets Management 
Branch (address above) written objections thereto. Each objection shall 
be separately numbered, and each

[[Page 37248]]

numbered objection shall specify with particularity the provisions of 
the regulation to which objection is made and the grounds for the 
objection. Each numbered objection on which a hearing is requested 
shall specifically so state. Failure to request a hearing for any 
particular objection shall constitute a waiver of the right to a 
hearing on that objection. Each numbered objection for which a hearing 
is requested shall include a detailed description and analysis of the 
specific factual information intended to be presented in support of the 
objection in the event that a hearing is held. Failure to include such 
a description and analysis for any particular objection shall 
constitute a waiver of the right to a hearing on the objection. Three 
copies of all documents shall be submitted and shall be identified with 
the docket number found in brackets in the heading of this document. 
Any objections received in response to the regulation may be seen in 
the Dockets Management Branch between 9 a.m. and 4 p.m., Monday through 
Friday.

VIII. References

    The following references have been placed on display in the Dockets 
Management Branch (address above) and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.
    1. Memorandum from the Food and Color Additives Review Section 
(HFF-415) to the Indirect Additives Branch (HFS-335) entitled ``FAP 
0B4201--Olin Corporation: Polyurethane resins from carboxyl-modified 
polyols as components of adhesives of coatings contacting foods: 
submission of 3-12-90,'' dated July 18, 1990.
    2. Kokoski, C. J., ``Regulatory Food Additive Toxicology'' in 
Chemical Safety Regulation and Compliance, edited by F. Homburger, 
J. K. Marquis, and S. Karger, New York, NY, pp. 24-33, 1985.
    3. Memorandum from the Chemistry Review Branch (HFS-247) to the 
Indirect Additives Branch (HFS-216) entitled ``FAP 0B4201 MATS# 
471): Newly Revised Exposure Estimate for Tolenediamine (TDA) from 
Polyurethane Adhesive Applications and Cumulative Exposure to TDA,'' 
dated March 2, 1993.
    4. ``Bioassay of 2,4-Diaminotoluene for Possible 
Carcinogenicity,'' National Cancer Institute. NCI-CG-TR-162, 1979.
    5. Report of the Quantitative Risk Assessment Committee entitled 
``FAP 0B4201: Upper Bound Lifetime Carcinogenic Risk from Exposure 
to Toluenediamine (TDA) from Polyurethane Adhesive Applications and 
Cumulative Exposure to TDA,'' dated June 14, 1996.

List of Subjects in 21 CFR Part 175

    Adhesives, Food additives, Food packaging.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, part 175 is 
amended as follows:

PART 175--INDIRECT FOOD ADDITIVES: ADHESIVES AND COMPONENTS OF 
COATINGS

    1. The authority citation for 21 CFR part 175 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 342, 348, 379e.

    2. Section 175.105 is amended in the table in paragraph (c)(5) by 
revising the entry for ``Polyurethane resins * * *'' under the heading 
``Substances'' to read as follows:


Sec. 175.105  Adhesives.

* * * * *
    (c) * * *
    (5) * * *

                                                                                                                
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                       Substances                                              Limitations                      
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  *                    *                    *                    *                    *                    *    
                                                             *                                                  
Polyurethane resins produced by: (1) reacting                                                                   
 diisocyanates with one or more of the polyols or                                                               
 polyesters named in this paragraph, or (2) reacting                                                            
 the chloroformate derivatives of one or more of the                                                            
 polyols or polyesters named in this paragraph with one                                                         
 or more of the polyamines named in this paragraph, or                                                          
 (3) reacting toluene diisocyanate or 4,4'                                                                      
 methylenebis(cyclohexylisocyanate) (CAS Reg. No. 5124-                                                         
 30-1) with: (i) one or more of the polyols or                                                                  
 polyesters named in this paragraph and with either N-                                                          
 methyldiethanolamine (CAS Reg. No. 105-59-9) and                                                               
 dimethyl sulfate (CAS Reg. No. 77-78-1) or                                                                     
 dimethylolpropionic acid (CAS Reg. No. 4767-03-7) and                                                          
 triethylamine (CAS Reg. No. 121-44-8), or (ii) a                                                               
 fumaric acid-modified polypropylene glycol or fumaric                                                          
 acid-modified tripropylene glycol), triethylamine (CAS                                                         
 Reg. No. 107-15-3), and ethylenediamine (CAS Reg. No.                                                          
 121-44-8), or (4) reacting meta-tetramethylxylene                                                              
 diisocyanate (CAS Reg. No. 2778-42-9) with one or more                                                         
 of the polyols and polyesters listed in this paragraph                                                         
 and with dimethylolpropionic acid (CAS Reg. No. 4767-                                                          
 03-7) and triethylamine (CAS Reg. No. 121-44-8), N-                                                            
 methyldiethanolamine (CAS Reg. No. 105-59-9), 2-                                                               
 dimethylaminoethanol (CAS Reg. No. 108-01-0), 2-                                                               
 dimethylamino-2-methyl-1-propanol (CAS Reg. No. 7005-                                                          
 47-2), and/or 2-amino-2-methyl-1-propanol (CAS Reg.                                                            
 No. 124-68-5).                                                                                                 
  *                    *                    *                    *                    *                    *    
                                                             *                                                  
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[[Page 37249]]

    Dated: June 30, 1998.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 98-18406 Filed 7-9-98; 8:45 am]
BILLING CODE 4160-01-F